Stage 2: UK114 HTTP404

As universally known, science is a lot of waiting. From mice studies to monotonous PCR cycles, the Colton lab runs plenty of patience-intensive projects that can seem daunting. Therefore, I should begin as soon as possible to avoid an incomplete or hastily patch-worked project for the summer, so theoretically like this week. Theoretically. Who knew just getting the supplies would cost the most time, as the day turnaround estimate for the UK114 mRNA clone to arrive stretched into its second week. But I haven’t just been dawdling about the lab for a week, that requires getting out of bed. Instead, I have been spending the week reading further into the specifics of the lab’s projects and prized focus: the methionine cycle.

The methionine cycle, in short, is an essential and widely used metabolic pathway in the body where the namesake amino acid is converted into SAM, a prevalent substrate used for methylation in an extensive list of processes. These systems include gene regulation, neurotransmitter production, amino acid conversion, and various protein mechanisms; but the Colton lab is particularly interested in the methylation of PP2A which has been shown to downregulate the phosphorylation of tau. This is extraordinary to Alzheimer’s research, as hyperphosphorylated tau composes the infamous tau tangles in the brain that drive the neurodegeneration seen in Alzheimer’s disease. Thus, it is suspected that the methionine re-synthesis step of the methionine cycle is inhibited, preventing the production of SAM and consequently the accumulation of phosphorylated tau. Indeed, this hypothesis is supported by the elevated presence of¬†homocysteine- a hazardous product of the methionine cycle that is normally recycled back into methionine -in many Alzheimer’s patients, suggesting some deficiency of the methionine synthesis step. While several factors are known to regulate this process, there are some intriguingly obscure proteins with unresearched functions that have a notably high presence in Alzheimer’s patients, such as RidA protein UK114.

Avoiding overly outlining the biochemistry and exact mechanisms of the methionine cycle and UK114’s potential interactions, my project involves the transfection of cells with the UK114 gene and subjugation of the cells to various conditions related to the methionine cycle to study UK114’s exact role in Alzheimer’s disease and why it is upregulated. I have spent the past week investigating much of UK114’s structural specifics and which enzymes it could potentially react with and when; however, I plan to test these theories for confirmation once I am able to produce a transient cell line expressing human UK114. Unfortunately, a delayed delivery that contained simply an empty vector without the sequence has put this plan at a standstill, but hopefully my project will commence at some point next week when the gene arrives. I feel like I have repeated this countlessly to everyone in my lab, but “until then, I’ll keep reading.”

Weekly Highlights:

“The methionine cycle is like a salmon wheel!” -Dr. Carol Colton
“A what”-Dang Nguyen as the lab meeting proceeds to derail into a half hour lecture on salmon wheels

“Did she just run outside and catch some wild ground squirrels for [brain] tissue samples?”-Christine O’Connell
“No. I don’t know. We should do that with hamsters.”-Dr. Carol Colton

“We should run into PetSmart and unlock all the hamster cages, so we can study them!”-Dr. Carol Colton

“Forget mice! We should go to New Zealand and study platypuses! And maybe hamsters.”-Dr. Carol Colton

“And here we see that- oh. That’s wrong. Oh well, it’s already in the grant!”-Dr. Carol Colton

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